Hydrogel-Based Novel Biomaterials: Achievements and Prospects

A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Applications".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 20226

Special Issue Editors


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Centro de Química Estrutural, Institute of Molecular Sciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1049-001 Lisboa, Portugal
Interests: controlled drug release; biomaterials characterization; biotribology; adsorption of biomolecules onto biomaterials; sterilization
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CiiEM – Interdisciplinary Research Center Egas Moniz, Instituto Universitário Egas Moniz, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal
Interests: polymers and polymeric systems; protein delivery; formulation in pediatrics; drug solubility enhancement; 3D-printing of pharmaceuticals
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Centro de Química Estrutural, Institute of Molecular Sciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1049-001 Lisboa, Portugal
Interests: hydrogels; drug delivery; biomaterial characterization; surface modification; wound dressings
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent decades, interest in hydrogels has increased, due to their vast biomedical and pharmaceutical applications. The similarity of these materials to many biological tissues and their unique behavior, resulting from their high water content, together with the possibility of tailoring their properties and/or ability to interact with cells by using an appropriate combination of monomers and synthesis methods, have placed them among the most promising biomaterials for different purposes. They have been used with success in areas such as injectable particulate systems, contact lenses, cartilage substitutes, catheter linings, valves, suture threads, wound-healing dressings, skin grafts, or biosensors. Their role has also become increasingly important in areas such as tissue engineering and regenerative medicine, or drug delivery and targeting.

Although a significant effort has been made to develop new hydrogels with improved properties and additional functionalities, several issues remain a challenge and have been targeted by intense research, combining knowledge of biology with materials engineering. For example, the design of hydrogels aims at those capable to respond to both local and systemic stimuli, with an in situ cross-linking/gelation capacity, adequate degradation rates or bioactive surfaces, which could allow for vascularization and a suitable tissue architecture and/or ability to avoid colonization by microorganisms. In a more transversal way, topics such as their ability to ensure a controlled and/or targeted release of drugs and other active agents, or their resistance to sterilization methods, have also been of concern.

This Special Issue aims to gather some of the most recent achievements and prospects related to the synthesis and processing of new, hydrogel-based biomaterials. Both original research and comprehensive review papers are welcome.

Dr. Ana Paula Serro
Dr. Ana Isabel Fernandes
Dr. Diana Silva
Guest Editors

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Keywords

  • hydrogels
  • biomaterials
  • smart materials
  • in situ gelation
  • biodegradation
  • drug release
  • tissue engineering
  • surface’s modifications
  • sterilization
  • cell culture
  • regenerative medicine
  • bio-recognition
  • wound dressings
  • tissue implants
  • scaffold

Published Papers (10 papers)

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Research

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20 pages, 5926 KiB  
Article
Exploring Functionalized Magnetic Hydrogel Polyvinyl Alcohol and Chitosan Electrospun Nanofibers
by Mónica Guerra, Fábio F. F. Garrudo, Célia Faustino, Maria Emilia Rosa and Maria H. L. Ribeiro
Gels 2023, 9(12), 968; https://doi.org/10.3390/gels9120968 - 11 Dec 2023
Viewed by 1086
Abstract
Nanofibrous materials present interesting characteristics, such as higher area/mass ratio and reactivity. These properties have been exploited in different applications, such as drug-controlled release and site-specific targeting of biomolecules for several disease treatments, including cancer. The main goal of this study was to [...] Read more.
Nanofibrous materials present interesting characteristics, such as higher area/mass ratio and reactivity. These properties have been exploited in different applications, such as drug-controlled release and site-specific targeting of biomolecules for several disease treatments, including cancer. The main goal of this study was to develop magnetized nanofiber systems of lysozyme (Lys) for biological applications. The system envisaged electrospun polyvinyl alcohol (PVA) and PVA/chitosan (CS) nanofibers, loaded with Lys, crosslinked with boronic acids [phenylboronic acid (PBA), including 2-acetylphenylboronic acid (aPBA), 2-formylphenylboronic (fPBA), or bortezomib (BTZ)] and functionalized with magnetic nanobeads (IONPs), which was successfully built and tested using a microscale approach. Evaluation of the morphology of nanofibers, obtained by electrospinning, was carried out using SEM. The biological activities of the Lys-loaded PVA/CS (90:10 and 70:30) nanofibers were evaluated using the Micrococcus lysodeikticus method. To evaluate the success of the encapsulation process, the ratio of adsorbed Lys on the nanofibers, Lys activity, and in vitro Lys release were determined in buffer solution at pH values mimicking the environment of cancer cells. The viability of Caco-2 cancer cells was evaluated after being in contact with electrospun PVA + Lys and PVA/CS + Lys nanofibers, with or without boronic acid functionalation, and all were magnetized with IONPs. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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15 pages, 1416 KiB  
Article
Development of Carvedilol Nanoformulation-Loaded Poloxamer-Based In Situ Gel for the Management of Glaucoma
by Bjad K. Almutairy, El-Sayed Khafagy and Amr Selim Abu Lila
Gels 2023, 9(12), 952; https://doi.org/10.3390/gels9120952 - 04 Dec 2023
Cited by 1 | Viewed by 945
Abstract
The objective of the current study was to fabricate a thermosensitive in situ gelling system for the ocular delivery of carvedilol-loaded spanlastics (CRV-SPLs). In situ gel formulations were prepared using poloxamer analogs by a cold method and was further laden with carvedilol-loaded spanlastics [...] Read more.
The objective of the current study was to fabricate a thermosensitive in situ gelling system for the ocular delivery of carvedilol-loaded spanlastics (CRV-SPLs). In situ gel formulations were prepared using poloxamer analogs by a cold method and was further laden with carvedilol-loaded spanlastics to boost the precorneal retention of the drug. The gelation capacity, rheological characteristics, muco-adhesion force and in vitro release of various in situ gel formulations (CS-ISGs) were studied. The optimized formula (F2) obtained at 22% w/v poloxamer 407 and 5% w/v poloxamer 188 was found to have good gelation capacity at body temperature with acceptable muco-adhesion properties, appropriate viscosity at 25 °C that would ease its ocular application, and relatively higher viscosity at 37 °C that promoted prolonged ocular residence of the formulation post eye instillation and displayed a sustained in vitro drug release pattern. Ex vivo transcorneal penetration studies through excised rabbit cornea revealed that F2 elicited a remarkable (p ˂ 0.05) improvement in CRV apparent permeation coefficient (Papp = 6.39 × 10−6 cm/s) compared to plain carvedilol-loaded in situ gel (CRV-ISG; Papp = 2.67 × 10−6 cm/s). Most importantly, in normal rabbits, the optimized formula (F2) resulted in a sustained intraocular pressure reduction and a significant enhancement in the ocular bioavailability of carvedilol, as manifested by a 2-fold increase in the AUC0–6h of CRV in the aqueous humor, compared to plain CRV-ISG formulation. To sum up, the developed thermosensitive in situ gelling system might represent a plausible carrier for ophthalmic drug delivery for better management of glaucoma. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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21 pages, 6860 KiB  
Article
The Effect of Gelatin Source on the Synthesis of Gelatin-Methacryloyl and the Production of Hydrogel Microparticles
by David Grijalva Garces, Luise Josephine Appoldt, Jasmin Egner, Nico Leister and Jürgen Hubbuch
Gels 2023, 9(12), 927; https://doi.org/10.3390/gels9120927 - 24 Nov 2023
Viewed by 1269
Abstract
Gelatin methacryloyl (GelMA) is widely used for the formulation of hydrogels in diverse biotechnological applications. After the derivatization of raw gelatin, the degree of functionalization (DoF) is an attribute of particular interest as the functional residues are necessary for crosslinking. Despite progress in [...] Read more.
Gelatin methacryloyl (GelMA) is widely used for the formulation of hydrogels in diverse biotechnological applications. After the derivatization of raw gelatin, the degree of functionalization (DoF) is an attribute of particular interest as the functional residues are necessary for crosslinking. Despite progress in the optimization of the process found in the literature, a comparison of the effect of raw gelatin on the functionalization is challenging as various approaches are employed. In this work, the modification of gelatin was performed at room temperature (RT), and eight different gelatin products were employed. The DoF proved to be affected by the bloom strength and by the species of gelatin at an equal reactant ratio. Furthermore, batch-to-batch variability of the same gelatin source had an effect on the produced GelMA. Moreover, the elasticity of GelMA hydrogels depended on the DoF of the protein as well as on bloom strength and source of the raw material. Additionally, GelMA solutions were used for the microfluidic production of droplets and subsequent crosslinking to hydrogel. This process was developed as a single pipeline at RT using protein concentrations up to 20% (w/v). Droplet size was controlled by the ratio of the continuous to dispersed phase. The swelling behavior of hydrogel particles depended on the GelMA concentration. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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19 pages, 10628 KiB  
Article
Self-Healing of Pluronic® F127 Hydrogels in the Presence of Various Polysaccharides
by Alexandra Lupu, Luiza Madalina Gradinaru, Daniela Rusu and Maria Bercea
Gels 2023, 9(9), 719; https://doi.org/10.3390/gels9090719 - 05 Sep 2023
Cited by 6 | Viewed by 1805
Abstract
Thermoresponsive Pluronic® F127 (PL) gels in water were investigated through rheological tests in different shear conditions. The gel strength was tuned with the addition of 1% polysaccharide solution. In the presence of xanthan gum (XG), the viscoelastic behavior of PL-based hydrogels was improved [...] Read more.
Thermoresponsive Pluronic® F127 (PL) gels in water were investigated through rheological tests in different shear conditions. The gel strength was tuned with the addition of 1% polysaccharide solution. In the presence of xanthan gum (XG), the viscoelastic behavior of PL-based hydrogels was improved in aqueous environment, but the rheological behavior was less changed with the addition of XG in PBS solutions, whereas in the presence of 0.1 M NaCl, the viscoelastic parameters decreased. PL micellar networks exhibited a self-healing ability, recovering their initial structure after applying cycles of high strain. The rheological characteristics of the PL hydrogel changed with the addition of 1% polysaccharides (xanthan gum, alginate, κ-carrageenan, gellan, or chitosan). PL/polysaccharide systems form temperature-responsive hydrogels with shear thinning behavior, yield stress, and self-healing ability, being considered a versatile platform for injectable biomaterials or bioinks. Thus, in the presence of xanthan gum in aqueous medium, the gel strength was improved after applying a high strain (the values of elastic modulus increased). The other investigated natural polymers induced specific self-healing behaviors. Good performances were observed with the addition of gellan gum, alginate, and κ-carrageenan, but for high values of strain, the ability to recover the initial structure decreased. A modest self-healing behavior was observed in the presence of chitosan and xanthan gum dissolved in NaCl solution. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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16 pages, 4129 KiB  
Article
Development of Natural Active Agent-Containing Porous Hydrogel Sheets with High Water Content for Wound Dressings
by Thanyaporn Pinthong, Maytinee Yooyod, Jinjutha Daengmankhong, Nantaprapa Tuancharoensri, Sararat Mahasaranon, Jarupa Viyoch, Jirapas Jongjitwimol, Sukunya Ross and Gareth M. Ross
Gels 2023, 9(6), 459; https://doi.org/10.3390/gels9060459 - 03 Jun 2023
Cited by 4 | Viewed by 2589
Abstract
This work was concerned with the fabrication of a porous hydrogel system suitable for medium to heavy-exudating wounds where traditional hydrogels cannot be used. The hydrogels were based on 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPs). In order to produce the porous structure, additional components were [...] Read more.
This work was concerned with the fabrication of a porous hydrogel system suitable for medium to heavy-exudating wounds where traditional hydrogels cannot be used. The hydrogels were based on 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPs). In order to produce the porous structure, additional components were added (acid, blowing agent, foam stabilizer). Manuka honey (MH) was also incorporated at concentrations of 1 and 10% w/w. The hydrogel samples were characterized for morphology via scanning electron microscopy, mechanical rheology, swelling using a gravimetric method, surface absorption, and cell cytotoxicity. The results confirmed the formation of porous hydrogels (PH) with pore sizes ranging from ~50–110 µm. The swelling performance showed that the non-porous hydrogel (NPH) swelled to ~2000%, while PH weight increased ~5000%. Additionally, the use of a surface absorption technique showed that the PH absorbed 10 μL in <3000 ms, and NPH absorbed <1 μL over the same time. Incorporating MH the enhanced gel appearance and mechanical properties, including smaller pores and linear swelling. In summary, the PH produced in this study had excellent swelling performance with rapid absorption of surface liquid. Therefore, these materials have the potential to expand the applicability of hydrogels to a range of wound types, as they can both donate and absorb fluid. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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20 pages, 5575 KiB  
Article
Pluronic® F127 Hydrogel Containing Silver Nanoparticles in Skin Burn Regeneration: An Experimental Approach from Fundamental to Translational Research
by Pedro Francisco, Mariana Neves Amaral, Afonso Neves, Tânia Ferreira-Gonçalves, Ana S. Viana, José Catarino, Pedro Faísca, Sandra Simões, João Perdigão, Adília J. Charmier, M. Manuela Gaspar and Catarina Pinto Reis
Gels 2023, 9(3), 200; https://doi.org/10.3390/gels9030200 - 06 Mar 2023
Cited by 2 | Viewed by 2181
Abstract
Presently, skin burns are considered one of the main public health problems and lack therapeutic options. In recent years, silver nanoparticles (AgNPs) have been widely studied, playing an increasingly important role in wound healing due to their antibacterial activity. This work is focused [...] Read more.
Presently, skin burns are considered one of the main public health problems and lack therapeutic options. In recent years, silver nanoparticles (AgNPs) have been widely studied, playing an increasingly important role in wound healing due to their antibacterial activity. This work is focused on the production and characterization of AgNPs loaded in a Pluronic® F127 hydrogel, as well as assessing its antimicrobial and wound-healing potential. Pluronic® F127 has been extensively explored for therapeutic applications mainly due to its appealing properties. The developed AgNPs had an average size of 48.04 ± 14.87 nm (when prepared by method C) and a negative surface charge. Macroscopically, the AgNPs solution presented a translucent yellow coloration with a characteristic absorption peak at 407 nm. Microscopically, the AgNPs presented a multiform morphology with small sizes (~50 nm). Skin permeation studies revealed that no AgNPs permeated the skin after 24 h. AgNPs further demonstrated antimicrobial activity against different bacterial species predominant in burns. A chemical burn model was developed to perform preliminary in vivo assays and the results showed that the performance of the developed AgNPs loaded in hydrogel, with smaller silver dose, was comparable with a commercial silver cream using higher doses. In conclusion, hydrogel-loaded AgNPs is potentially an important resource in the treatment of skin burns due to their proven efficacy by topical administration. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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22 pages, 4608 KiB  
Article
Effects of Non-Conventional Sterilisation Methods on PBO-Reinforced PVA Hydrogels for Cartilage Replacement
by Tomás Pires, Andreia Sofia Oliveira, Ana Clara Marques, Madalena Salema-Oom, Célio G. Figueiredo-Pina, Diana Silva and Ana Paula Serro
Gels 2022, 8(10), 640; https://doi.org/10.3390/gels8100640 - 09 Oct 2022
Cited by 1 | Viewed by 2142
Abstract
Articular cartilage (AC) degradation is a recurrent pathology that affects millions of people worldwide. Polyvinyl alcohol (PVA) hydrogels have been widely explored for AC replacement. However, their mechanical performance is generally inadequate, and these materials need to be reinforced. Moreover, to be used [...] Read more.
Articular cartilage (AC) degradation is a recurrent pathology that affects millions of people worldwide. Polyvinyl alcohol (PVA) hydrogels have been widely explored for AC replacement. However, their mechanical performance is generally inadequate, and these materials need to be reinforced. Moreover, to be used in a clinical setting, such materials must undergo effective sterilisation. In this work, a PVA hydrogel reinforced with poly(p-phenylene-2,6-benzobisoxazole) (PBO) nanofibres was submitted to three non-conventional sterilisation methods: microwave (MW), high hydrostatic pressure (HHP), and plasma (PM), in order to evaluate their impact on the properties of the material. Sterilisation was achieved in all cases. Properties such as water content and hydrophilicity were not affected. FTIR analysis indicated some changes in crystallinity and/or crosslinking in all cases. MW was revealed to be the most suitable method, since, unlike to PM and HHP, it led to a general improvement of the materials’ properties: increasing the hardness, stiffness (both in tensile and compression), and shear modulus, and also leading to a decrease in the coefficient of friction against porcine cartilage. Furthermore, the samples remained non-irritant and non-cytotoxic. Moreover, this method allows terminal sterilisation in a short time (3 min) and using accessible equipment. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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14 pages, 4442 KiB  
Article
Formulation and Evaluation of Diclofenac Potassium Gel in Sports Injuries with and without Phonophoresis
by Komal Ammar Bukhari, Imran Ahmad Khan, Shahid Ishaq, Muhammad Omer Iqbal, Ali M. Alqahtani, Taha Alqahtani and Farid Menaa
Gels 2022, 8(10), 612; https://doi.org/10.3390/gels8100612 - 26 Sep 2022
Cited by 2 | Viewed by 2982
Abstract
Background: Pain remains a global public heath priority. Phonophoresis, also known as sonophoresis or ultrasonophoresis, is when an ultrasound is used to maximize the effects of a topical drug. Purpose: The objective of this study was to test, in patients injured in [...] Read more.
Background: Pain remains a global public heath priority. Phonophoresis, also known as sonophoresis or ultrasonophoresis, is when an ultrasound is used to maximize the effects of a topical drug. Purpose: The objective of this study was to test, in patients injured in sports or accidents (N = 200), the efficacy of diclofenac potassium (DK) 6%, 4%, and 2% formulated gels with and without phonophoresis in comparison with market available standard diclofenac sodium (DS or DN) gel. Methods: The patients were enrolled after informed consent. By using the lottery method, 100 patients were randomly segregated into five groups without phonophoresis and repeated similarly with phonophoresis at a frequency of 0.8 MHz, an intensity of about 1.5 W/cm2, and at continuous mode (2:1). Group-1 was treated with 6% DK gel, group-2 was treated with 4% DK gel, group-3 was treated with 2% DK gel, group-4 was treated with 4% DS gel and group-5 was given control gel three to four times a week for 4 weeks. The patients were screened by using NPRS and WOMAC scales. They were assessed on the baseline, 4th session, 8th session, 12th session, and 16th session. Results: Significant dose-dependently relief was observed in NPRS (Numeric Pain Rating Scale) and the WOMAC (Western Ontario McMaster Osteo-Arthritis) index for pain in disability and stiffness for each group treated with DK gel compared to DS gel. Phonophoresis increased these benefits significantly when used after topical application of DK gel or DS gel, and the dose-dependent effects of DK gel plus phonophoresis were stronger than the dose-dependent effects of DS gel plus phonophoresis. The faster and profounder relief was due to phonophoresis, which allows more penetration of the DK gel into the skin as compared to the direct application of DK gel in acute, uncomplicated soft tissue injury, such as plantar fasciitis, bursitis stress injuries, and tendinitis. In addition, DK gel with phonophoresis was well tolerated. Thus, in this personalized clinical setting, according to the degree of inflammation or injured-induced pain, disability, and stiffness, DK gel 6% with phonophoresis appeared more effective and thus more recommendable than DS gel 6% alone or DS gel 6% combined to phonophoresis. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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Review

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46 pages, 5115 KiB  
Review
Hydrogels in Cutaneous Wound Healing: Insights into Characterization, Properties, Formulation and Therapeutic Potential
by Mariana Ribeiro, Marco Simões, Carla Vitorino and Filipa Mascarenhas-Melo
Gels 2024, 10(3), 188; https://doi.org/10.3390/gels10030188 - 08 Mar 2024
Viewed by 1294
Abstract
Hydrogels are polymeric materials that possess a set of characteristics meeting various requirements of an ideal wound dressing, making them promising for wound care. These features include, among others, the ability to absorb and retain large amounts of water and the capacity to [...] Read more.
Hydrogels are polymeric materials that possess a set of characteristics meeting various requirements of an ideal wound dressing, making them promising for wound care. These features include, among others, the ability to absorb and retain large amounts of water and the capacity to closely mimic native structures, such as the extracellular matrix, facilitating various cellular processes like proliferation and differentiation. The polymers used in hydrogel formulations exhibit a broad spectrum of properties, allowing them to be classified into two main categories: natural polymers like collagen and chitosan, and synthetic polymers such as polyurethane and polyethylene glycol. This review offers a comprehensive overview and critical analysis of the key polymers that can constitute hydrogels, beginning with a brief contextualization of the polymers. It delves into their function, origin, and chemical structure, highlighting key sources of extraction and obtaining. Additionally, this review encompasses the main intrinsic properties of these polymers and their roles in the wound healing process, accompanied, whenever available, by explanations of the underlying mechanisms of action. It also addresses limitations and describes some studies on the effectiveness of isolated polymers in promoting skin regeneration and wound healing. Subsequently, we briefly discuss some application strategies of hydrogels derived from their intrinsic potential to promote the wound healing process. This can be achieved due to their role in the stimulation of angiogenesis, for example, or through the incorporation of substances like growth factors or drugs, such as antimicrobials, imparting new properties to the hydrogels. In addition to substance incorporation, the potential of hydrogels is also related to their ability to serve as a three-dimensional matrix for cell culture, whether it involves loading cells into the hydrogel or recruiting cells to the wound site, where they proliferate on the scaffold to form new tissue. The latter strategy presupposes the incorporation of biosensors into the hydrogel for real-time monitoring of wound conditions, such as temperature and pH. Future prospects are then ultimately addressed. As far as we are aware, this manuscript represents the first comprehensive approach that brings together and critically analyzes fundamental aspects of both natural and synthetic polymers constituting hydrogels in the context of cutaneous wound healing. It will serve as a foundational point for future studies, aiming to contribute to the development of an effective and environmentally friendly dressing for wounds. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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15 pages, 903 KiB  
Review
Injectable Poloxamer Hydrogels for Local Cancer Therapy
by Ana Camila Marques, Paulo Cardoso Costa, Sérgia Velho and Maria Helena Amaral
Gels 2023, 9(7), 593; https://doi.org/10.3390/gels9070593 - 24 Jul 2023
Cited by 4 | Viewed by 2313
Abstract
The widespread push to invest in local cancer therapies comes from the need to overcome the limitations of systemic treatment options. In contrast to intravenous administration, local treatments using intratumoral or peritumoral injections are independent of tumor vasculature and allow high concentrations of [...] Read more.
The widespread push to invest in local cancer therapies comes from the need to overcome the limitations of systemic treatment options. In contrast to intravenous administration, local treatments using intratumoral or peritumoral injections are independent of tumor vasculature and allow high concentrations of therapeutic agents to reach the tumor site with minimal systemic toxicity. Injectable biodegradable hydrogels offer a clear advantage over other delivery systems because the former requires no surgical procedures and promotes drug retention at the tumor site. More precisely, in situ gelling systems based on poloxamers have garnered considerable attention due to their thermoresponsive behavior, biocompatibility, ease of preparation, and possible incorporation of different anticancer agents. Therefore, this review focuses on the use of injectable thermoresponsive hydrogels based on poloxamers and their physicochemical and biological characterization. It also includes a summary of these hydrogel applications in local cancer therapies using chemotherapy, phototherapy, immunotherapy, and gene therapy. Full article
(This article belongs to the Special Issue Hydrogel-Based Novel Biomaterials: Achievements and Prospects)
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